Synthesis of 1,3-disubstituted naphthalenes from the Baylis-Hillman acetates with the aid of manganese(III) acetate

Article abstract of DOI:10.1016/S0040-4039(02)00884-5

1,3-Disubstituted naphthalene derivatives can be easily synthesized from Baylis-Hillman acetates by successive reaction: (1) S_N2' type reaction with diethyl malonate or ethyl nitroacetate; (2) manganese(III) acetate-assisted radical cyclization

Full text of DOI:10.1016/S0040-4039(02)00884-5

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 4675–4678
Synthesis of 1,3-disubstituted naphthalenes from the
Baylis–Hillman acetates with the aid of manganese(III) acetate
Yang Jin Im,a Ka Young Lee,a Taek Hyeon Kimb and Jae Nyoung Kima,*
aDepartment of Chemistry and Institute of Basic Science, Chonnam National University, Kwangju 500-757, South Korea
bFaculty of Applied Chemistry, Chonnam National University, Kwangju 500-757, South Korea
Received 7 February 2002; revised 15 March 2002; accepted 2 May 2002
Abstract—1,3-Disubstituted naphthalene derivatives can be easily synthesized from Baylis–Hillman acetates by successive reaction:
(1) SN2% type reaction with diethyl malonate or ethyl nitroacetate; (2) manganese(III) acetate-assisted radical cyclization and (3)
aromatization with NaI/O2 system or elimination of nitrous acid. © 2002 Elsevier Science Ltd. All rights reserved.
The Mn(III)- and Ce(IV)-induced homolytic malonyla-
tion1 or nitroalkylation2 of aromatic compounds has
been studied extensively.1,2 The reaction might occur as
depicted in Scheme 1. The intramolecular version of the
reaction can also be carried out. Thus, malonate deriva-
tives with aromatic ring at the d-position would give
tetrahydro- or dihydro-naphthalenes depending on
their structure.1g,1j,1k
via the successive SN2%–SNAr elimination strategy.4 In
the previous paper there must be a halogen atom at the
ortho position of the benzaldehyde moiety.
In order to shed more light on the facile synthesis of
naphthalenes4 and to generalize our previous methodol-
ogy, we focused our attention on the synthesis of
naphthalenes from Baylis–Hillman adducts derived
from benzaldehydes without a ortho-halogen sub-
stituent. Thus, we tried the Mn(III)- or Ce(IV)-assisted
cyclization of malonate derivatives with aromatic ring
at the d-position, which could be prepared easily from
the reaction of diethyl malonate and the Baylis–Hill-
man acetates of benzaldehydes. As shown in Scheme 2
and in Table 1, the reaction of 1a and diethyl malonate
in the presence of K2CO3 in acetonitrile gave 2a in 81%
yield.5 The reaction of 2a with Mn(OAc)3 (6 equiv.) in
Regioselective synthesis of naphthalene derivatives has
been and continues to be of great interest in organic
synthesis.3 A new synthetic procedure is still highly
desired due to the abundance of the skeleton in many
biologically important natural products.3,4 Recently we
have reported on the synthesis of naphthalenes from
the reaction of the Baylis–Hillman acetates derived
from o-halobenzaldehydes and primary nitro alkanes
COOR
COOR
+
+
Mn(OAc)2
HOAc
+
Mn(OAc)3
COOR
COOR
COOR
COOR
COOR
COOR
+
Ar
Ar-H
H
COOR
COOR
COOR
COOR
COOR
COOR
Mn(OAc)3
- H+
Ar
H
Ar
Ar
- Mn(OAc)2
- ACO-
H
Scheme 1.
Keywords: Baylis–Hillman acetate; naphthalene; manganese(III) acetate; malonyl radical.
* Corresponding author. Fax: 82-62-530-3389; e-mail: kimjn@chonnam.chonnam.ac.kr
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)00884-5

4676
Y. J. Im et al. / Tetrahedron Letters 43 (2002) 4675–4678
OAc
EWG
COOEt
EWG
R
COOEt
COOEt
1. Mn(OAc)3, EtOH
(2. NaI, O2, DMF)
R
CH3CN, K2CO3
1
2
4 R
EWG = COOEt, COOMe, NO2
R = COOEt, COOMe, CH3
- HNO2
Mn(OAc)3
COOEt
(EWG = NO2)
NaI/O2
(EWG = COOEt, COOMe)
GWE
R
1. decarbalkoxylation
2. autoxidation
3
Scheme 2.
ethanol gave the dihydronaphthalene derivative 3a in
66% isolated yield. The use of CAN (cerium ammo-
nium nitrate) for the conversion of 2a into 3a was less
effective than the use of Mn(OAc)3 in view of yield and
unfavorable formation of many side products. Conver-
sion of 3a to the naphthalene derivative was carried out
with a NaI/O2 system1i in DMF to give 4a in 70% yield.
With these results in hand we extended the reaction
toward various combinations and the results are sum-
marized in Table 1. In other cases (entries 2–4) we did
not separate the intermediacy dihydronaphthalenes 3.
Crude 3 was used in the next oxidation step without
purification. As shown in entry 2, dimethyl malonate
derivative 2b showed similar results.
We extended the reaction with primary nitro alkane
derivatives, which were known to undergo the Mn(III)-
assisted radical coupling to arenes.2a,b In these cases
naphthalene derivatives were obtained directly in good
yields (entries 5–9). The aromatization step was not
necessary when we used nitro compounds. Elimination
of nitrous acid from the intermediacy dihydronaph-
thalenes might occur in the reaction conditions directly,
as depicted in Scheme 2.
A typical procedure for the synthesis of 5a and the
selected spectroscopic data was mentioned in Ref. 5.
Extension of this methodology to the synthesis of vari-
ous heterocycles by using the Baylis–Hillman acetates
derived from heterocyclic aldehydes is currently
underway.
The reaction mechanism for the formation of dihy-
dronaphthalene 3a and its conversion to naphthalene
4a is depicted in Scheme 3. Generation of malonyl
radical I, addition to aromatic ring and coupling with
acetoxy radical to give II, elimination of acetic acid
furnished 3a. Successive decarbalkoxylation and
autoxidation6 of 3a gave the naphthalene 4a.1i,6 It is
uncertain at this stage which step proceeds first, decar-
balkoxylation or autoxidation. Further studies on the
reaction mechanism for the conversion of 3a to 4a are
in progress.
Acknowledgements
This work was supported by the grant (No. R02-2000-
00074) from the Basic Research Program of the Korea
Science & Engineering Foundation.
COOEt
Mn(OAc)3
CH2(COOEt)2
Mn(OAc)3
1a
2a
COOEt
EtOH, reflux
CH3CN, K2CO3
- Mn(OAc)2
COOEt
I
OAc
COOEt
NaI/O2, DMF, 120 oC
- AcOH
3a
4a
1. decarbalkoxylation
2. autoxidation
EtOOC COOEt
II
Scheme 3.

Y. J. Im et al. / Tetrahedron Letters 43 (2002) 4675–4678
Table 1. Synthesis of 1,3-disubstituted naphthalenes 4a–f
4677
entry
1
product
yield (mp)
substrate
COOEt
COOEt
COOEt
COOEt
COOMe
conditions
1. Mn(OAc)3 (6 equiv)
EtOH, reflux, 48 h (66%)
COOEt
46%
(38-39 oC)
2. O2/NaI, DMF
120 oC, 24 h (70%)
4a
2a
2b
2c
2d
2e
COOEt
COOEt
1. Mn(OAc)3 (6 equiv)
EtOH, reflux, 48 h
49%
(46-47 oC)
2
2. O2/NaI, DMF
120 oC, 6 h
4b
4c
4d
4a
COOMe
COOMe
COOEt
1. Mn(OAc)3 (6 equiv)
EtOH, reflux, 48 h
COOEt
COOEt
COOEt
51%
(87-88 oC)
3
2. O2/NaI, DMF
120 oC, 24 h
Cl
Cl
COOEt
COOEt
1. Mn(OAc)3 (6 equiv)
EtOH, reflux, 48 h
COOEt
COOEt
COOEt
37%
(oil)
4
5
2. O2/NaI, DMF
120 oC, 24 h
COOEt
COOEt
COOEt
NO2
64%
60%
80%
Mn(OAc)3 (4 equiv)
EtOH, reflux, 48 h
COOEt
COOEt
COOEt
COOEt
NO2
Mn(OAc)3 (4 equiv)
EtOH, reflux, 48 h
6
Cl
Cl
4c
2f
COOEt
COOEt
COOEt
COOEt
NO2
Mn(OAc)3 (4 equiv)
EtOH, reflux, 48 h
7
8
9
4d
COOEt
2g
COOEt
EtOOC
COOEt
COOEt
NO2
47%a
(108-109 oC)
Mn(OAc)3 (4 equiv)
EtOH, reflux, 48 h
4e
COOEt
2h
2i
COOEt
NO2
COOEt
67%
(51-52 oC)
Mn(OAc)3 (6 equiv)
EtOH, reflux, 48 h
4f
CH3
CH3
aTrace amounts (3%) of diethyl 2,4-anthracene dicarboxylate was isolated.
References
1989, 54, 2713; (h) Iqbal, J.; Bhatia, B.; Nayyar, N. K.
Chem. Rev. 1994, 94, 519; (i) Santi, R.; Bergamini, F.;
Citterio, A.; Sebastiano, R.; Nicolini, M. J. Org. Chem.
1992, 57, 4250; (j) Citterio, A.; Sebastiano, R.; Marion, A.;
Santi, R. J. Org. Chem. 1991, 56, 5328; (k) Snider, B. B.
Chem. Rev. 1996, 96, 339 and further references cited
therein.
1. (a) Tsai, A.-I.; Wu, Y.-L.; Chuang, C.-P. Tetrahedron
2001, 57, 7829; (b) Jiang, M.-C.; Chuang, C.-P. J. Org.
Chem. 2000, 65, 5409; (c) Baciocchi, E.; Muraglia, E. J.
Org. Chem. 1993, 58, 7610; (d) Baciocchi, E.; Dell’Aira,
D.; Ruzziconi, R. Tetrahedron Lett. 1986, 27, 2763; (e)
Kim, Y. H.; Lee, D. H.; Yang, S. G. Tetrahedron Lett.
1995, 36, 5027; (f) Citterio, A.; Santi, R.; Fiorani, T.;
Strologo, S. J. Org. Chem. 1989, 54, 2703; (g) Citterio, A.;
Fancelli, D.; Finzi, C.; Pesce, L.; Santi, R. J. Org. Chem.
2. (a) Chuang, C.-P.; Wu, Y.-L.; Jiang, M.-C. Tetrahedron
1999, 55, 11229; (b) Kurz, M. E.; Ngoviwatchai, P.;
Tantrarant, T. J. Org. Chem. 1981, 46, 4668; (c) Kurz, M.
E.; Ngoviwatchai, P. J. Org. Chem. 1981, 46, 4672.

4678
Y. J. Im et al. / Tetrahedron Letters 43 (2002) 4675–4678
3. (a) Seong, M. R.; Song, H. N.; Kim, J. N. Tetrahedron
Lett. 1998, 39, 7101 and further references cited therein;
(b) Rucker, M.; Bruckner, R. Synlett 1997, 1187.
h. After usual workup and column chromatographic
purification process (hexane/ether, 8:1) 5a was obtained as
a white solid (36 mg, 70%).
1
2a: 81%; clear oil; H NMR (CDCl3) l 1.15 (t, J=7.2 Hz,
4. Kim, J. N.; Im, Y. J.; Gong, J. H.; Lee, K. Y. Tetrahedron
6H), 1.34 (t, J=7.2 Hz, 3H), 3.20 (d, J=7.8 Hz, 2H), 3.79
(t, J=7.8 Hz, 1H), 3.98–4.15 (m, 4H), 4.27 (q, J=7.2 Hz,
2H), 7.25–7.38 (m, 5H), 7.77 (s, 1H); 13C NMR (CDCl3) l
13.79, 14.13, 26.15, 50.42, 60.87, 61.18, 127.83, 128.14,
128.46, 129.01, 134.92, 141.44, 167.32, 168.72.
Lett. 2001, 42, 4195.
5. Typical procedure for the synthesis of 2a, 3a and 5a and
their selected spectroscopic data are as follows: To a
stirred solution of Baylis–Hillman acetate 1a (1.0 g, 4.0
mmol) and diethyl malonate (710 mg, 4.4 mmol) in aceto-
nitrile (10 mL) was added potassium carbonate (620 mg,
4.5 mmol). The reaction mixture was stirred at room
temperature for 20 h. After usual workup and column
chromatographic purification process (hexane/ether, 8:1)
2a was obtained as an oil (1.13 g, 81%). The stereochem-
istry of 2a is E as in the previous report.4 Trace amounts
(ca. 5%) of the corresponding Z form were contaminated.
A stirred mixture of 2a (100 mg, 0.287 mmol) and man-
ganese(III) acetate dihydrate (115 mg, 0.43 mmol) in dry
ethanol (4 mL) was heated to reflux for 48 h. Additional
manganese(III) acetate (115 mg×3, 1.29 mmol) was added
three times during the reaction. The reaction mixture was
filtered through a Celite pad and washed with ethanol.
After usual workup and column chromatographic purifica-
tion process (hexane/ether, 8:1) 3a was obtained as an oil
(66 mg, 66%). A stirred solution of 3a (66 mg, 0.19 mmol)
and sodium iodide (86 mg, 0.57 mmol) in DMF (3 mL)
was heated to 120°C under an oxygen atmosphere for 24
3a: 66%; clear oil; IR (KBr) 1733, 1713, 1634 cm−1 1H
;
NMR (CDCl3) l 1.25 (t, J=7.1 Hz, 6H), 1.35 (t, J=7.1
Hz, 3H), 3.34 (d, J=1.5 Hz, 2H), 4.19–4.32 (m, 6H),
7.26–7.37 (m, 4H), 7.51 (s, 1H); 13C NMR (CDCl3) l
13.99, 14.30, 29.89, 59.17, 60.89, 62.09, 126.95, 127.84,
128.56, 128.88, 129.87, 131.98, 132.91, 135.60, 166.30,
170.36.
5a: 70%; white solid, mp 38–39°C; IR (KBr) 2984, 2937,
1
1721 cm−1; H NMR (CDCl3) l 1.47 (t, J=7.1 Hz, 3H),
1.49 (t, J=7.1 Hz, 3H), 4.51 (q, J=7.1 Hz, 2H), 4.48 (q,
J=7.1 Hz, 2H), 7.60–7.75 (m, 2H), 8.01 (d, J=8.2 Hz,
1H), 8.73 (s, 1H), 8.75 (s, 1H), 8.93 (d, J=8.6 Hz, 1H); 13
C
NMR (CDCl3) l 14.31 (2C), 61.26, 61.32, 125.86, 126.56,
126.83, 127.93, 129.21, 129.81, 129.88, 133.10, 133.14,
135.34, 165.84, 166.92.
6. (a) Jeffrey, A. M.; Jerina, D. M. J. Am. Chem. Soc. 1972,
94, 4048; (b) Hock, H.; Depke, F. Chem. Ber. 1950, 83,
327.